Thrombogenicity of intravenous 5-fluorouracil alone or in combination with cisplatin.
Acute myocardial infarction was observed in two patients receiving standard intravenous doses of 5-fluorouracil (5-FU)-based chemotherapy. Therefore, the authors prospectively assessed the thrombogenicity of this agent by studying ten patients, six with head and neck cancer and four with gastrointestinal malignancies, receiving 5-FU (1 g/m2/day) as a constant intravenous infusion over a 4-day or 5-day period. The six patients with head and neck cancer also received a single dose of 100 mg/m2 of cisplatin on day 1. Blood samples were obtained preinfusion, 24 hours into the infusion, and postinfusion. Samples were assayed for fibrinopeptide A (FpA) by enzyme-linked immunoassay, for protein C activity (PCa) using a chromogenic substrate (Spectrozyme PCa), and protein C (PCag) and free protein S antigen (PSag) by electroimmunoassay. No patient experienced a thrombotic event. A significant increase was observed in FpA levels during the infusion which returned toward baseline at the conclusion of the infusion. After infusion of 5-FU, the PCa value was significantly lower than the PCag (37 +/- 17 versus 69 +/- 24%; P less than 0.002). No effect on protein S was observed. The changes in the patients receiving 5-FU alone were comparable to those who also received CDDP. The authors conclude that during the infusion of 5-FU, the rise in FpA activation and reduction in PCa as compared to PCag are compatible with activation of coagulation.
Kuzel
T
T
Section of Hematology/Oncology, Northwestern University Medical School, Chicago, IL 60611.
Esparaz
B
B
Green
D
D
Kies
M
M
D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage*; D005340:Fibrinogen / Q000032:analysis*; D005344:Fibrinopeptide A / Q000032:analysis*; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced*; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis; D014062:Tongue Neoplasms / Q000188:drug therapy
D011486:Protein C; D005344:Fibrinopeptide A; D005340:Fibrinogen; D002945:Cisplatin; D005472:Fluorouracil